Nouveau traitement pour la prostate.

Researchers have discovered that a marker found on aggressive prostate cancer cells could also be used as a way to guide treatments to the cancer, according to new research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool.

The molecule, called NAALADL2, is already measured to see if prostate cancer is likely to return, but the new study has shown that it can also help direct treatment to the cancer.

The team, based at UCL, had already found that prostate cancer cells have more of the NAALADL2 molecule on their surface compared to cells from healthy tissue. Prostate cancer patients whose tumour cells have high levels of this molecule are more than twice as likely to see their disease return following surgery.

In the new study, the researchers attached the drug saporin to an antibody targeted against NAALADL2 to destroy prostate cancer cells in the lab.

Dr Hayley Luxton, lead researcher from the Molecular Diagnostics and Therapeutics Laboratory at University College London, said: "Using antibodies mounted with a toxic payload, we can exploit the fact that aggressive prostate cancer cells have more NAALADL2.

"The next step is to further develop this for use in patients, which we hope can be done in a relatively short timeframe."

Around 46,500 men are diagnosed with prostate cancer in the UK each year. And around 11,000 men will die from the disease each year.

The study was funded by The Urology Foundation, John Black Charitable Trust and Cancer Research UK.

Louise de Winter, CEO of The Urology Foundation, said: "This research was attractive to us as something that could potentially distinguish those so-called 'pussy cat' cancers from the 'tigers'. We're very excited by the potential shown and look forward to further findings."

Dr Chris Parker, Chair of the NCRI's Prostate Cancer Clinical Studies Group, said: "When it comes to aggressiveness, prostate cancer can either be slow-growing or much faster to grow and spread. And there is an urgent need to find better treatments for the more aggressive version of the disease.

"Interestingly, this study shows that the very marker that indicates a prostate tumour may be more aggressive, could also be the key to its downfall."

The Notch signaling pathway could be playing a role in the spread of prostate cancer to other organs and tissues, according to recent research, opening a new avenue of treatment using Notch signaling inhibitors.

This specific pathway has been shown to be faulty in several types of cancer, and is an important system mediating communication between neighboring cells. It plays a major role during embryonic development and neural differentiation and function.

“Most previous studies on the role that Notch plays in prostate cancer were performed in cultured cells in the laboratory. These studies produced contradictory results. Some studies concluded that Notch was an oncogene, that it promoted cancer development, and others that it was a tumor suppressor gene,” Dr. Li Xin, associate professor of molecular and cellular biology at Baylor College of Medicine, and senior author of the study, said in a press release. “To gain a better understanding of Notch in prostate cancer we decided to study its role in an animal model in a defined genetic context.”

The team used a mouse model of prostate cancer that failed to express a tumor suppressor gene called Pten in their prostate. Xin’s team had previously found there was an inverse correlation between Notch activity and the expression on the Pten gene. In other words, when the expression of Pten went up, the activity of Notch went down, and vice-versa.

The researchers saw that mice without Pten in their prostate (and therefore with overactive Notch signaling), prostate tumors spread to other major organs such as the lungs and the liver, revealing that Notch signaling could activate tumor spread, or metastasis.

The researchers further showed that Notch signaling was likely driving metastasis by upregulating another molecule called FoxC2. When they blocked FoxC2, the Notch-mediated spread of the tumor was reduced.

For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel. For example, docetaxel is commonly used as the "first-line" therapy, while cabazitaxel is used as the "second-line" therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied. This week, however, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Center may change the perspective on a role for combination chemotherapy in advanced disease.

The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin -- a type of platinum chemotherapy -- in patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, 160 men have been randomized to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.

To monitor the effects of treatment, MD Anderson researchers tracked several variables including Progression Free Survival, as well as changes in blood levels of prostate-specific antigen (PSA) and bone-specific alkaline phosphatase (BAP, a marker of prostate cancer in bone cells). In addition, safety and toxicity were monitored for both patient groups.

Analysis and comparison of the data demonstrated that median PFS was significantly longer for patients receiving combination versus single agent chemotherapy (6.7 months vs 4.4 months, respectively, p = 0.01). Furthermore, reductions in both PSA and BAP were greater for the combination therapy group. PSA reductions greater than 50 percent occurred 60 percent of the time with combined chemotherapy vs. 44 percent with the single drug. PSA reductions greater than 90 percent occurred 28 percent of the time with two chemotherapy drugs vs. 20 percent with one. In addition, BAP reductions greater than 50 percent for combination vs. single drug were 63 percent and 25 percent respectively.

Side effects, such as fatigue, anemia and neutropenia were comparable for both the single-drug regimen and two-drug regimen. In addition, there were no significant toxicity events.

"We believe cabazitaxel-carboplatin combination chemotherapy may become the clinical standard for advanced prostate cancer once additional safety, efficacy and overall survival data is generated," explained Paul Corn, M.D., Ph.D., an associate professor of genitourinary medical oncology at MD Anderson. "Dr. Ana Aparicio's lab is currently developing tumor-specific biomarkers to identity patients with an aggressive variant of prostate cancer most likely to benefit from this approach."

John Alderete, a professor at Washington State University's School of Molecular Biosciences, says the trichomoniasis parasite activates a suite of proteins, the last of which makes sure the proteins stay active.

Alderete and colleagues at WSU and Washington University in St. Louis report their findings in the recent PLoS Pathogens.

Caused by a protozoan parasite, trichomoniasis is often referred to as the most common curable sexually transmitted infection. However, most infected people have no symptoms, so it often goes untreated.

"Most women, it's the Number One sexually transmitted infection," says Alderete. "We're going to have at least 10 million women infected this year and an equal number of men because they all get infected if they come into contact with an infected partner."

Infected women have a greater risk of pregnancy complications and HIV. Infected men have a 40 percent greater chance of developing prostate cancer, according to a 2006 study led by Siobhan Sutcliffe, a Washington University epidemiologist and co-author of the recent PLoS Pathogens paper.

This latest study, she says, "is providing a molecular mechanism that might explain that association."

Much of the study was done in a single building, WSU's Biotechnology and Life Sciences Building, and involved two of the more accomplished researchers on the Pullman campus.

"This is just coincidence. I've only been here five years," says Alderete. "And when I arrived here five years ago, I had no clue that we would be going in this kind of direction. But the more I read and the more we talked in the hallways, the more it became clear that, wait a minute, we may have something here between us."

WSU cancer researcher Nancy Magnuson is an expert on the protein PIM1, a promoter of cancer cell growth, and identified the protein in the cascade of proteins leading from trichomoniasis to prostate cancer. WSU molecular biologist Ray Reeves brought to bear his expertise in HMGA1. The protein turns genes on and off and ended up being the actor making sure other proteins in the trichomoniasis-to-cancer sequence stay on.

Alderete hopes knowledge of the mechanism will lead to better diagnosis and treatment.

Prostate cancer is generally treated as if it's a single disease. But researchers have discovered a new type of the cancer that appears to affect 15 percent of patients, a finding that paves the way for better diagnosis and more targeted therapies down the road.

The new pathway for prostate cancer development was discovered after a team of scientists identified unique mutations in a gene known as SPOP (pronounced 'S-Pop') while examining patient tumors. These aberrations may lead to a dangerous accumulation of proteins that spark tumor growth, forming a distinct kind of cancer, according to the study, published in the journal Nature Genetics.

(Feb. 5, 2009) — Scientists at Melbourne's Burnet Institute have developed a potential new treatment for patients with prostate cancer. An article, which described the invention, has recently been published in The Journal of Clinical Investigation.

Head of the Burnet Institute's Cancer Immunotherapy Laboratory, Associate Professor Pei Xiang Xing said his group has produced a monoclonal antibody to a unique tumour marker for the treatment of prostate cancer. The monoclonal antibody is directed at cancer-producing cells carrying the specific molecule known as PIM-1, which is responsible for cell survival, proliferation and differentiation. Over-expression of PIM-1 plays a critical role in the development, progression and metastasis of prostate cancer and other cancers such as leukaemia. The monoclonal antibody significantly inhibited cancer cell growth when used in laboratory models of prostate cancer.

Professor Xing's group demonstrated that the monoclonal antibody binds to PIM-1 present in cancer cells and creates a chain of events leading to the death of the cells. In particular, the therapeutic effect was improved by combination of the antibody with other drugs currently used to treat prostate cancer.

Director of the Burnet Institute, Professor Brendan Crabb said that while the therapy was still in its early days this was the first time that researchers had found a treatment that targeted prostate cancer cells with a specific antibody to PIM-1 and which resulted in the death of the malignant cells and a reduction in tumour size.

"This is an exciting step in the development of new treatments for patients with prostate cancer with very promising laboratory-test results," Professor Crabb said.